Molecular modeling methods outline
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Molecular Mechanics
Can be used for molecules containing more than 1000 atoms.
Fast procedure to perform conformational analysis.
Computation of geometry, enthalpy, entropy and vibrational
states.
Energy of a molecule is described as the sum of contributions
arising from distortions of ideal bond distance, bond angles,
dihedral angles, and non-bonded iterations.
Experimental analogies are electron diffraction and gas phase
chromatography
MMFF (molecular mechanics force field)
o Bond lengths often differ from experimental values by 0.01.
o Parameters not developed for inorganic systems.
o May reproduce trends in dipoles but values are way off.
SYBYL
 Parameterized for second row or greater elements
 Does well with organic but poorly with inorganic.
 Results are very inaccurate for some systems.
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Semi empirical (quantum based methods)
Useful for molecules containing up to 200 atoms.
Calculations are based upon molecular orbital theory.
Uses a simplified version of Schrödinger’s equation.
Calculations only use valence shells. Inner shells are treated as a
fixed core.
Will provide accurate models of a molecule if the atoms making up
the molecule are included in the data set.
Useful for equilibrium geometries: transition metal inorganic and
organo-metalic compounds.
Interaction among nuclei and electrons and molecular geometry in
terms of minimum energy arrangements of nuclei.
Total electron density: corresponds to the electron density measured
in an x-ray diffraction experiment.
AM1
Gives poor results for second row elements
PM3
Was specifically developed for equilibrium geometries of transition
metal inorganic and organo-metallic compounds.
Reasonably good results for metal-carbon bond lengths.
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Hartree-Fock
Impractical for molecules with greater than 100 atoms
Useful for thermodynamic and kinetic comparisons.
Provides excellent account of molecular equilibrium and
transition state geometry.
Does well with equilibrium conformations.
Calculations use a simplification of the Schrödinger’s equation.
A single wave function Ψ serves as a replacement (or product)
of many electron wave functions Ф. Each electron is
considered to be effected by the sum of all other electrons.
Incomplete description of coupling motions of electrons
(electron correlation). Often causes greater errors in transition
metal inorganic and organo-metallic compounds.
Electron-electron repulsion may be overestimated, resulting in
shorter reported bond lengths.
Poor for bond making and breaking reactions.
Moderately successful in reproducing dipole trends but the
magnitudes of the dipoles are often overestimated.
Hartree-Fock approximation : involves a single determinant of
products of one-electron functions
Spin orbital written as a product of a space part Ψ which is
a function of the coordinates of a single electron
Molecular orbital has two possible spin parts α and β, only
2 electrons may occupy given molecular orbital and they
must have opposite spins.
Size comparison of dipole values. Smallest to largest values.
STO-3G < 6-31G* approx= 6-311+G(2D,P) < 6-31G(*)
3-21G, 6-31G, and 6-311G
Function representing valence regions are split into
components
Inner and outer shell orbitals used.
6-31G, 6-31G*, and 6-31G**
Polarization basis sets
Allows for small displacement of the center of electronic
charge.
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STO-3G
Uses 3 Gaussian type orbitals to estimate 1 Slater Type
Orbital
Has high errors for hypervalent compounds
Bond lengths are longer than experimental values.
Minimal basis set. Uses only the number of functions
required to represent all of the electrons of the atom.
H and He use 1 function
Li and Be use 2 functions.
Properly accounts for O and N compounds but not P and
S compounds.
3-21G
Bond lengths are longer than experimental values.
Superior to STO-3G in regards to bond length and
ordering bond distance.
6-31G*
Superior to STO-3G in regards to bond length and
ordering bond distance.
Results are approximately equal to 6-311+G which
indicates that 6-31G* may represent the limit for HartreeFock calculations.
3-21G*
Good for structure determination of 2nd row elements.
3-21G(*)
Has a basis set for second row and heavier group
elements
Good for structure determination of 2nd row elements.
Similar to 3-21G but has d-type functions add on second
row and heavier elements.
Yields dipole results higher than expected, but will give
improved results with a basis extension set.
6-31G
Often have significant error in bond length.
6-31+G*
Basis sets incorporate diffuse functions.
Useful for calculations involving anions.
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Diffuse functions are added to some atoms for
calculations.
6-311+G - Yields dipole results higher than expected.
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Density functional
o Most processor intensive of all the methods.
o Electron correlation taken into account explicitly.
o Uses numerical integration that may cause greater magnitudes
of uncertainties.
o Accounts explicitly for many-electron effects by including a
correlation term based on an idealized many electron problem.
o Calculations should be superior to Hartree-Fock and
comparable to mp2
o Treats a molecule as a functional of the electron density.
o Treats the molecule as an energy functional of the molecular
system. The energy functional is a combination of the following
energy components: Kinetic energy of electrons, Attraction of
electrons by the nuclear potential and electron interaction,
classical Coulomb repulsion of charge density, and an
exchange correlation term that accounts for many body and
quantum effects.
o Local Density Approximation is reduced to one-electron
densities in Density Functional Theory. Good results are
produced from atoms with large or constant electron densities,
such as metals and transition metals.
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